TY - JOUR
T1 - Mitochondrial DNA copy-number variation and pancreatic cancer risk in the prospective EPIC cohort
AU - Gentiluomo, Manuel
AU - Katzke, Verena A.
AU - Kaaks, Rudolf
AU - Tjønneland, Anne
AU - Severi, Gianluca
AU - Perduca, Vittorio
AU - Boutron-Ruault, Marie Christine
AU - Weiderpass, Elisabete
AU - Ferrari, Pietro
AU - Johnson, Theron
AU - Schulze, Matthias B.
AU - Bergmann, Manuela
AU - Trichopoulou, Antonia
AU - Karakatsani, Anna
AU - Vecchia, Carlo La
AU - Palli, Domenico
AU - Grioni, Sara
AU - Panico, Salvatore
AU - Tumino, Rosario
AU - Sacerdote, Carlotta
AU - Bueno-De-Mesquita, Bas
AU - Vermeulen, Roel
AU - Sandanger, Torkjel M.
AU - Ramón Quirós, J.
AU - Rodriguez-Barranco, Miguel
AU - Amiano, Pilar
AU - Colorado-Yohar, Sandra
AU - Ardanaz, Eva
AU - Sund, Malin
AU - Khaw, Kay Tee
AU - Wareham, Nicholas J.
AU - Schmidt, Julie A.
AU - Jakszyn, Paula
AU - Morelli, Luca
AU - Canzian, Federico
AU - Campa, Daniele
N1 - Funding Information:
We thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study. This work was partially supported by intramural funds of University of Pisa and DKFZ, by Fondazione Tizzi, and by Fondazione Arpa (www.fondazionearpa.it). The EPIC-Potsdam study was funded by the Federal Ministry of Education and Research (Germany), the German Cancer Aid, the German Cancer Research Center, and the German Institute of Human Nutrition Potsdam-Rehbru€cke. EPIC-Oxford was supported by Cancer Research UK (C8221/A19170) and the Medical Research Council UK (MR/M012190/1). EPIC-Greece was supported by the Hellenic Health Foundation.
Funding Information:
We thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study. This work was partially supported by intramural funds of University of Pisa and DKFZ, by Fondazione Tizzi, and by Fondazione Arpa (www.fondazionearpa.it). The EPIC-Potsdam study was funded by the Federal Ministry of Education and Research (Germany), the German Cancer Aid, the German Cancer Research Center, and the German Institute of Human Nutrition Potsdam-Rehbrücke. EPIC-Oxford was supported by Cancer Research UK (C8221/A19170) and the Medical Research Council UK (MR/M012190/1). EPIC-Greece was supported by the Hellenic Health Foundation.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020
Y1 - 2020
N2 - Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results: We observed lower mtDNA copy number with advancing age (P = 6.54 x 10-5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16-0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07-0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses. Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk. Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.
AB - Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited. Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results: We observed lower mtDNA copy number with advancing age (P = 6.54 x 10-5) and with a high body mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.16-0.79; P = 0.01] when comparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 (95% CI, 0.07-0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses. Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk. Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.
UR - https://www.scopus.com/pages/publications/85081094265
U2 - 10.1158/1055-9965.EPI-19-0868
DO - 10.1158/1055-9965.EPI-19-0868
M3 - Article
C2 - 31932413
AN - SCOPUS:85081094265
SN - 1055-9965
VL - 29
SP - 681
EP - 686
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 3
ER -
SDG 3 Good Health and Well-being